The proposed research will consist of the application of nmr spectroscopy to the examination of a hierarchy of problems in biological chemistry. The problems to be examined deal with the molecular basis of biological activity, in peptides and proteins. The conformations of tetrapeptides through to exhibit strong stereochemical preferences which arise as a result of a single amino acid substitution will be measured. Experiments will be performed to determine whether predicted effects of the postulated mechanism of enzyme action of trypsin can be observed. The complex of trypsin and the inhibitor will be studied. All of the above projects will be related to one another and the results will be interpreted in terms of the major themes of protein folding and conformational determinants of biological activity. In pursuing the proposed research many of the nmr techniques will be used in unique ways. The developments of C13 difference spectroscopy, lanthanide induced shift measurements and tetrapeptide correlation time interpretations will all involve fundamental application of nmr in the peptide and protein field. It is expected that all of these studies will be applicable to a large number of significant biological problems beyond this program.